A detrimental role of RelB in mature oligodendrocytes during experimental acute encephalomyelitis
| Autor: | La Shardai N. Brown, Michael Marone, Angela S. Gupta, Ulrich Siebenlist, Andrew Hoskins, Debolina D. Biswas, Karli Mockenhaupt, Tomasz Kordula |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Encephalomyelitis Autoimmune Experimental Encephalomyelitis Immunology Inflammation RelB Biology lcsh:RC346-429 NF-κB Mice 03 medical and health sciences Cellular and Molecular Neuroscience chemistry.chemical_compound 0302 clinical medicine Neural Stem Cells Conditional gene knockout medicine Demyelinating disease Animals lcsh:Neurology. Diseases of the nervous system EAE Oligodendrocytes Research General Neuroscience RELB Multiple sclerosis Transcription Factor RelB Experimental autoimmune encephalomyelitis NF-kappa B Brain medicine.disease 3. Good health Oligodendroglia 030104 developmental biology Neurology chemistry Astrocytes Cancer research medicine.symptom 030217 neurology & neurosurgery |
| Zdroj: | Journal of Neuroinflammation Journal of Neuroinflammation, Vol 16, Iss 1, Pp 1-13 (2019) |
| ISSN: | 1742-2094 |
| Popis: | Background Multiple sclerosis (MS) is an autoimmune demyelinating disease of the central nervous system (CNS). It is firmly established that overactivation of the p65 (RelA) nuclear factor kappa B (NF-κB) transcription factor upregulates expression of inflammatory mediators in both immune and non-immune resident CNS cells and promotes inflammation during MS. In contrast to p65, NF-κB family member RelB regulates immune cell development and can limit inflammation. Although RelB expression is induced during inflammation in the CNS, its role in MS remains unknown. Methods To examine the role of RelB in non-immune CNS cells, we generated mice with RelB specifically deleted in astrocytes (RelBΔAST), oligodendrocytes (RelBΔOLIGO), or neural progenitor-derived cells (RelBΔNP). We used experimental autoimmune encephalomyelitis (EAE), an accepted mouse model of MS, to assess the effect of RelB deletion on disease outcomes and performed analysis on the histological, cellular, and molecular level. Results Despite being a negative regulator of inflammation, conditional knockout of RelB in non-immune resident CNS cells surprisingly decreased the severity of EAE. This protective effect was recapitulated by conditional deletion of RelB in oligodendrocytes but not astrocytes. Deletion of RelB in oligodendrocytes reduced disease severity, promoted survival of mature oligodendrocytes, and correlated with increased activation of p65 NF-κB. Conclusions These findings suggest that RelB fine tunes inflammation and cell death/survival during EAE. Importantly, our data points out the detrimental role RelB plays in controlling survival of mature oligodendrocytes, which could be explored as a viable option to treat MS in the future. Electronic supplementary material The online version of this article (10.1186/s12974-019-1548-7) contains supplementary material, which is available to authorized users. |
| Databáze: | OpenAIRE |
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